Implementation

The implementation of the micro-iterative method described here must be flexible enough to permit the different possibilities on the sizes between the two regions, its interaction and on the number of micro-iterations at every alternating process.

Schematically the flux diagram can be depicted as follows:

• Firstly the geometry is read from the input. The set of atoms that belong to the core and environment zones must be specified (the hydrogen link atom will always be at zone where its QM-host belongs). When any of the described approximated interaction between the core and the environment is chosen the core zone must include at least all the QM zone. In addition any geometrical restriction can be imposed.
• A first full energy QM/MM is performed in order to evaluate the gradient norms of the different zones.
• Decide what process to do first (TS search in core / minimization of environment) and how many iterations can be carried out.
• Here starts a conditional loop that will not stop until both optimizations fulfill the convergence criteria or the maximum number of iterations is reached.
• When TS search in core starts the procedure is the same as described in section 3.1. There will be only one initial Hessian calculation and this matrix will be updated during the whole process. It will be a full Hessian rather than the one (square+vector) depicted in figure 3.1 in page .
• For the minimization the L-BFGS optimization is activated. When ESP/MM or 1SCF/MM approximations are set a first full QM/MM energy must be carried out in order to calculate the ESP charges from the electron density or to save the one-electron and two-electron integrals.

For a more detailed description of the implementation and subroutines see the appendix section B in page .